Biotechnology - Genomic and Proteomics/Data, narratives and tools produced by the BGP field

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Answer the questions:

  1. This section aims to define what kind of data, narratives and tools constitute the outputs of the field and its dynamics. This will assit to adress issues like what is the impact of making data open and what are the design principles (e.g.: data in science may get better if open once it receives annotations and can be improved by other scientist).

Data

File:FundDataMap.jpg

  • Foundational Data
    • Big players:
  • Observational Data
    • Big Players:

BGP Company Profiles - Data For more information on these companies, see: BGP Company Profiles - Data and BGP Table of Biggest For-Profit Companies

Narratives

BGP Company Profiles - Narratives



Tools

Biological Materials

Biological Materials are any material, natural or man-made, that comprises whole or part of a living structure or biomedical device, such the ones listed below.

Excluded from our focus are the Experimental model organisms, such as chickens, dogs or frogs, since these species may not necessarily be genetically amenable (i.e. they may have long generation intervals and poor genetic maps) but they have other experimental advantages. These species are widely used model organisms in developmental biology.

Stem cells

Concept and purpose:

Steam cells are cells with the ability to divide for indefinite periods in culture and to give rise to specialized and different cell types. In addition, in many tissues they serve as a sort of internal repair system, dividing essentially without limit to replenish other cells as long as the person or animal is still alive. Stem cells are distinguished from other cell types by two important characteristics. First, they are unspecialized cells capable of renewing themselves through cell division, sometimes after long periods of inactivity. Second, under certain physiologic or experimental conditions, they can be induced to become tissue- or organ-specific cells with special functions.

From the NIH Stem Cell Basics Site:

  1. What are stem cells, and why are they important?
  2. What are the unique properties of all stem cells?
  3. What are embryonic stem cells?
  4. What are adult stem cells?
  5. What are the similarities and differences between embryonic and adult stem cells?
  6. What are induced pluripotent stem cells?
  7. What are the potential uses of human stem cells and the obstacles that must be overcome before these potential uses will be realized?
  8. Where can I get more information?

Initial issues regarding enclosure of these resource:

"University of Wisconsin researcher James Thomson and his colleagues wowed the scientific community when they reported in November 1998 that they had isolated and cultured human embryonic stem cells.1 They also precipitated intense debate. Although moral dilemmas and federal funding of stem-cell research have received the most media attention, behind-the-scenes concern has centered on the market for stem cells — the ownership, control, pricing, and availability of stem-cell lines. For many academic researchers hoping to build on Thomson's discovery, the difficulty of obtaining stem cells was immensely frustrating.

This difficulty arose because not only did Wisconsin have material rights to the cell lines its researchers generated, but Thomson had filed U.S. patent applications on his discoveries, resulting in intellectual property rights. These latter rights, owned by the University of Wisconsin and managed by its technology-transfer office, the Wisconsin Alumni Research Foundation (WARF), encompassed both Thomson's stem cells and the core techniques used to develop them. For this reason, these rights governed research on almost all available human embryonic stem-cell lines." (Murray, 2007)

Plasmid

Concept and purpose:

A plasmid is an extrachromosomal DNA element separate from the chromosomal DNA and found in almost bacteria species, which is capable of replicating independently of the chromosomal DNA. In form, they are double-stranded, DNA molecules. Some plasmids can be inserted into a bacterial chromosome, where they become a permanent part of the bacterial genome. It is here that they provide great functionality in molecular science.

They can be integrated into mammalian genomes, thereby conferring to mammalian cells whatever genetic functionality they carry. Thus, this gives you the ability to introduce genes into a given organism by using bacteria to amplify the hybrid genes that are created in vitro. This tiny but mighty plasmid molecule is the basis of recombinant DNA technology.

Plasmids used in genetic engineering are called vectors (a vector is a DNA molecule used as a vehicle to transfer foreign genetic material into another cell). Plasmids serve as important tools in genetics and biotechnology labs, where they are commonly used to multiply (make many copies of) or express particular genes. Many plasmids are commercially available for such uses.

Worms

Concept and Purpose:

If you've got a sequence from the human genome, the next question is ‘What does the sequence mean?’. One means by which to answer the question is to inactivate specific genes in model organisms such as worms. For instance, the nematode worm Caenorhabditis elegans is a very simple animal but it shares many genes and molecular pathways with humans.

Fruit flies

Concept and purpose:

The fruit fly (Drosophila melanogaster) is a small insect that feeds and breeds on spoiled fruit. It has been used as a model organism for over 100 years and thousands of scientists around the world work on it.

As with most of the long-established model organisms, the initial choice was for practical reasons. The fruit fly is small and has a simple diet. Therefore, large numbers of flies can be maintained inexpensively in the laboratory. The life cycle is also very short, taking about two weeks, so large-scale crosses can be set up and followed through several generations in a matter of months. Fruit flies also have large polytene chromosomes, whose barcode patterns of light and dark bands allow genes to be mapped accurately.

Due to these advantages, fruit flies were extensively used in the early 20th century to work out the principles of genetics. Indeed, they are still used in this capacity to teach genetics in schools.

Mice

Concept and purpose:

The mouse is the model organism most closely related to humans.

Regardless of their genetic or experimental advantages and disadvantages, certain species are chosen as model organisms because they occupy a pivotal position in the evolutionary tree or because some quality of their genome makes them ideal to study. Another consideration that must be addressed is the relevance of model organisms to humans. Surprisingly, over 60 per cent of the human disease genes that have been identified thus far have counterparts in the fly and worm, revealing a core of about 1500 gene families that is conserved in all animals.

However, genes affecting more evolutionarily advanced features, such as our immune system, are less likely to have direct counterparts in simple beings. For these systems, we require closer models such as the mouse. in this sense, Mice called genomic model organisms. The mouse genome is similarly organized to the human genome and large blocks of genes are even arranged in the same order.

The suitability of mice for genetic analysis is enhanced by the availability of different species, which can be used for inter-specific crosses. The advantage of this approach is that the different species are likely to have different DNA sequences in the genome. Therefore, the hybrids produced from such crosses can be used to make finely detailed genetic maps. Large-scale crosses can therefore be carried out to accurately map disease genes.

As if the above were not enough, the mouse also has a string of unique technological advantages. Gene transfer technology is highly advanced, so transgenic mice can be created carrying any foreign gene of interest. Also, the mouse is the only vertebrate species in which pre-selected genes can be deliberately mutated in a precise manner (see Knockout mice below). This means it is possible to create exact replicas of the genetic defects that cause diseases in humans. For some reason, certain complex diseases are difficult to replicate in the mouse and in such cases the rat is often a suitable alternative.

A great deal has been learned about humans by mapping and isolating mouse genes and using these as a short cut to find corresponding human genes. Mice have been extensively used to establish disease models by mimicking the gene defects seen in humans, and these models can be used to test the efficacy of new drugs.

Types of Mouse used in Biotechnology:

  • SPONTANEOUS MOUSE
    • Research:
    • Funds:
    • Patent: not subject to patents
    • Patent Owner: N/A
    • Use: general research tool
    • Historic of patent license strategy: N/A
    • Biobank:
    • Results on Innovation:
  • KNOCK-OUT MOUSE
    • Research: University of Utah
    • Funds:
    • Patent:
    • Patent Owner: University of Utah
    • Use: general purpose research tool
    • How it works: How do Knockout mice work?
    • Historic of patent license strategy: "the University of Utah received a patent in 1987 but never sought to enforce the patent against follow-on researchers using the knock-out methodology. Instead, Knock-out mice were made available at (essentially) marginal cost through the Jackson Laboratory (i.e., these mice were distributed as JAX mice)." (pg 12) (Murray at all 2009)
    • Biobank: Jax Labs
    • Results on Innovation:
  • ONCO-MOUSE
    • Research: Harvard
    • Funds: partially financed by DuPont and public fund of ???
    • Development: Internally by DuPont
    • Patent:
    • Patent Owner: DuPont
    • Use:general purpose research tool
    • Historic of patent license strategy: "As a result of their partial funding of Harvard's Oncomouse discoveries and their internal development of Cre-Lox technology, DuPont gained exclusive control over patents for these two technologies. In contrast to the University of Utah, DuPont exercised strict control over the distribution and use of mice that exploited the techniques covered by their patent portfolio. During the early 1990s, researchers (and their institutions) who wanted "freedom to operate" were obliged to obtain a license from DuPont when they sought to receive and use an Onco or Cre-Lox mouse.The detailed licensing agreement required annual disclosure to DuPont regarding experimental progress, limits on informal mouse exchange among academic researchers, and "reach through" rights allowing DuPont to automatically receive licensing revenue from any commercial applications developed using either Cre-Lox or Onco technology." (pg 12) (Murray at all 2009)
    • Community reaction to patent license strategy and high transaction costs of legal access and lack of "freedom to operate" exception:
      • protest: patent invalidation proceedings (which did not work)
      • informality: formation of VIP sharing networks in the shadow of most University's official policy rules and under the constant possibility of law suits
      • institutional reaction toward openness: Jax Laboratory made mice available without the necessity of a license
      • institutional reaction toward closedness (fear): restrictions from Universities on researches advising the non-use of the mice - University's official policy rules
      • redundant development: development of mice during the research process, bringing high costs (time - delays of 18 months were reported by Murray 2009 and money)
      • new research lines: researches that saw barriers to access the mice took new directions (Murray 2009)
    • Biobank: Jax Labs
    • Results on Innovation before NIH MoU: Delay on research for almost 2 years were faced here. Plus, since these are general purpose technologies, high potential to impact vertical and horizontal academic research.
    • Results on Policy: NIH MoU and others see: NIH EFFORTS
    • Results on Innovation after NIH MoU: Vertically, an average increase of citations of 21% (pg 23). Horizontally, average increase of 25% of new last-authors citations, average of 20% citations from new institutions and 20% increase on diversity of key words (pg 23-26) (Murray at all 2009)
  • CRE-LOX MOUSE
    • Research: Harvard, partially financed by DuPont
    • Funds: partially financed by DuPont and public fund of ???
    • Development: Internally by DuPOnt
    • Patent:
    • Patent Owner: DuPont
    • Use: general purpose research tool
    • Historic of patent license strategy: same as "Onco-Mouse"
    • Community reaction to patent license strategy and high transaction costs of legal access and lack of "freedom to operate" exception: same as Onco-Mouse, with exception for the access through Jax Labs (see Murray at all, pg 27 for more detailed analysis). So, higher dependence in VIPs and resulting higher transaction costs (eg: requisites of co-authorship).
    • Biobank: Jax Labs
    • Results on Innovation: similar to Onco-mouse
    • Results on Policy: NIH MoU and others see: NIH EFFORTS
    • Results on Innovation after NIH MoU: Vertically, an average increase of citations of 18% (pg 23) Horizontally, average increase of 22% of new last-authors citations, average of 20% citations from new institutions and 30% increase on diversity of key words (pg 23-26) (Murray at all 2009)

Software

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